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University of Groningen Diamond magnetometry for sensing in biological environment Perona Martinez, Felipe

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University of Groningen

Diamond magnetometry for sensing in biological environment

Perona Martinez, Felipe

DOI:

10.33612/diss.111974782

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.

Document Version

Publisher's PDF, also known as Version of record

Publication date: 2020

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Perona Martinez, F. (2020). Diamond magnetometry for sensing in biological environment. Rijksuniversiteit Groningen. https://doi.org/10.33612/diss.111974782

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1

Introduction

T

heir crystal clear appearance, surrounded by a glare of colourful rays of light have captured the attention of people since thousands of years ago. Today, diamonds offer much more than their aesthetic beauty. They are a crucial element in our technology. Because of their extensive list of physical properties, diamonds are found in a wide range of devices, from drill bits to sophisticated sensors.

Biomedicine has been taking advantages of the diamond’s properties for different purposes. The hardness of the diamond has been used to extend the lifetime of implants[1]. Its biocompatibility has been exploited to build substrates for growing diverse cell types such as fibroblasts[2], HeLa cells and osteoblasts[3]. Its stable chemical surface has been used to carry molecules in drug delivery devices[4].

Although the highly organised structure of the diamond lattice is re-sponsible for most of its physical properties, the defects found in the crys-tal enable it with additional optical attributes. One of this defect is the Nitrogen-Vacancy center (NV center). The NV center is a point defect occurring in the crystal lattice of diamonds, it consists of a vacancy with one atom of nitrogen substituting carbon in two adjacent lattice sites. This configuration presents exceptional optical properties. First, it is photolu-minescent, it emits one red photon after being exited by a green one. This means that it is possible to measure a small magnetic field by measuring a large optical signal that is related to it. Since optical signals are easier to measure and can be measured more sensitively, we achieve many orders of magnitude better sensitivities[5, 6] than with conventional MRI. Moreover, the intensity of photoluminescence is modulated by a magnetic moment present at the same location of the NV center. This attribute is the basic concept behind Diamond Magnetometry (DM), i.e. measuring magnetic field through NV centers in diamonds.

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INTRODUCTION

research the implementation of Diamond Magnetometry to detect (oxygen) free radical inside living cells.

The main hypothesis that sustains the idea of detecting of (oxygen) free radicals by diamond magnetometry is the fact that the missing electron of the radical grants a magnetic moment to the molecule, which interacts with the NV centers allowing its detection. The research presented in this book has proven that this hypothesis is true, but also it has yielded additional knowledge about the interaction of nanodiamonds with biomolecules and cells.

The intention of focusing the application of diamond magnetometry to detect (oxygen) free radicals is to overcome the limitations present in the current measuring techniques.

The cell produces Oxygen Free Radicals (OFR) in a regulated physio-logical process, but the loss of balance between its production and clear-ance is associated with oxidative stress, which triggers the development of pathologies[7]. The research of that relationship has linked the altered reg-ulation of OFR with the origin of cancer, cardiovascular diseases, diabetes and neurological disorders[8].

Considering the key role that OFR play, it is of great importance to im-prove the pool of resources available for their study. Diamond magnetome-try offers the possibility to fill the gaps that other techniques cannot resolve. The use of nanodiamonds implanted with NV centers allows measuring at nanometric scale, at a diffraction-limited resolution. This attribute might allow determining the oxidative stress of a cell at specific places. Moreover, the NV center also offers to improve the time resolution, allowing real-time measuring.

The works collected in this volume can be seen as landmarks over the path that has been built during the prosecution of the PhD project. Un-der that point of view, this book reflects how the Diamond magnetometry technique has been developed in our laboratories. Starting from funda-mental questions, such as: “How to place the nanodiamonds inside the cells?” or “Is the functionalization of the nanodiamonds interfering with their magneto-optical properties?”, we progressed to actually use the NV centers hosted in the nanodiamonds as sensors of magnetic noise, which we can use to detect and measure chemical reactions in inert samples or even in living cells.

Each chapter of this book reports important scientific contributions to the field of Diamond Magnetometry (DM) applied to cell biology, but also they show implicitly the state of the technical development of this technique in our facilities. To be able to operate over the NV center we have

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designed and built the magnetometers, we have programmed the control system that coordinates the instrumentation and all the software needed to operate the new device. Also, the analysis of the photoluminescent signal was completely built in house as part of my work as PhD student. Albeit the similitude of our system with the standard magnetometer used in the community, the biological nature of our samples, and the use of ensembles of NV centers in nanodiamonds, instead of bulk diamonds, set particular restrictions and considerations that make our system unique.

At the time when this book was printed, two of its chapters were already published in a high impact journal, and a third one was under peer-review evaluation in another important journal. Chapter 2 explores the use of recombinant proteins as coatings for nanodiamonds. The study is centred on the effect of the coatings in the colloidal stability of the nanoparticles, and the influence of these coatings in the particle uptake of two different cell lines. In Chapter 3 an innovative application for nanodiamonds is proposed. The investigations started by determining the proteins that at-tach stronger to the surface of the untreated nanodiamond, then we have determined that several of these proteins match with biomarkers used to detect diseases. These results suggest the use of nanodiamonds to deplete high abundant proteins from a sample. Chapter 4 presents the first re-sults of using Diamond Magnetometry to detect a free radical produced in real-time under physiological conditions. This is an important landmark towards the measurement of free radical inside cells. Finally, Chapter 5 discusses the implications of these investigations, how are they related and how this research enables further developments in diamond magnetometry.

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INTRODUCTION

References

[1] M. D. Fries and Y. K. Vohra, “Nanostructured diamond film deposi-tion on curved surfaces of metallic temporomandibular joint implant,” Journal of Physics D: Applied Physics, vol. 35, no. 20, 2002.

[2] B. Shi, Q. Jin, L. Chen, and O. Auciello, “Fundamentals of ultra-nanocrystalline diamond (UNCD) thin films as biomaterials for develop-mental biology: Embryonic fibroblasts growth on the surface of (UNCD) films,” Diamond and Related Materials, vol. 18, no. 2-3, pp. 596–600, 2009.

[3] P. Bajaj, D. Akin, A. Gupta, D. Sherman, B. Shi, O. Auciello, and R. Bashir, “Ultrananocrystalline diamond film as an optimal cell inter-face for biomedical applications,” Biomedical Microdevices, vol. 9, no. 6, pp. 787–794, 2007.

[4] R. A. Shimkunas, E. Robinson, R. Lam, S. Lu, X. Xu, X. Q. Zhang, H. Huang, E. Osawa, and D. Ho, “Nanodiamond-insulin complexes as pH-dependent protein delivery vehicles,” Biomaterials, vol. 30, no. 29, pp. 5720–5728, 2009.

[5] L. Ciobanu, D. A. Seeber, and C. H. Pennington, “3D MR microscopy with resolution 3.7 µm by 3.3 µm by 3.3 µm,” Journal of Magnetic Resonance, vol. 158, no. 1-2, pp. 178–182, 2002.

[6] P. Glover and S. P. Mansfield, “Limits to magnetic resonance mi-croscopy,” Reports on Progress in Physics, vol. 65, no. 10, pp. 1489– 1511, 2002.

[7] W. Dr¨oge, “Free radicals in the physiological control of cell function,” Physiological Reviews, vol. 82, no. 1, pp. 47–95, 2002.

[8] M. Valko, D. Leibfritz, J. Moncol, M. T. Cronin, M. Mazur, and J. Telser, “Free radicals and antioxidants in normal physiological func-tions and human disease,” International Journal of Biochemistry and Cell Biology, vol. 39, no. 1, pp. 44–84, 2007.

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